Acute Myeloid Leukemia (AML)Phase 1NCT02071927
Study of the Glutaminase Inhibitor CB-839 in Leukemia
A Phase 1 study testing CB-839 and CB-Aza in people with Acute Myeloid Leukemia (AML) and Acute Lymphocytic Leukemia (ALL), run by Calithera Biosciences, Inc at 5 sites in United States.
Trial summary
Many tumor cells, in contrast to normal cells, have been shown to require the amino acid glutamine to produce energy for growth and survival. To exploit the dependence of tumors on glutamine, CB-839, a potent and selective inhibitor of the first enzyme in glutamine utilization, glutaminase, will be tested in this… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL)
- What is being tested?
- CB-839 and CB-Aza
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 5 sitesUnited States
- Study dates
- Mar 2014to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of AML or ALL, relapsed or refractory after at least 1 prior treatment regimen. Newly-diagnosed patients ≥ 60 years old who have refused or are considered unfit for standard chemotherapy regimens or stem cell transplantation are also eligible.
- Patients must have no available approved therapies that confer clinical benefit
- All patients must have bone marrow involvement of their tumor, with documented blast percentage of > 5%.
- Peripheral blood blast count must be ≤ 30,000 cells/µL.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
- Adequate hepatic, renal, and cardiac function
Who cannot join
- Any other current malignancy
- Patients with acute promyelocytic leukemia (APL)
- Treatment with an unapproved, investigational agent within 21 days of the first dose of study drug
- Allogeneic hematopoietic stem cell transplant or Donor Lymphocyte Infusion within 90 days prior to to the first dose of study drug
- Active GVHD
- Unable to receive medications by mouth
Show all 11Show fewer
- Major surgery within 28 days before Cycle 1 Day 1
- Uncontrolled, active infection; patients who are known to have HIV infection/ seropositivity, Hepatitis A, B, or C, or CMV reactivation
- Significant neurotoxicity/neuropathy (Grade 3 or higher) within 14 days prior to Day 1
- Refractory nausea and vomiting or other situation that may preclude adequate absorption
- Conditions that could interfere with treatment and procedures
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
Colorado Blood Cancer Institute
Denver, Colorado, 80218
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
About this study
Official title: A Phase 1 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Oral Doses of the Glutaminase Inhibitor CB-839 in Patients With Relapsed and/or Treatment-Refractory Leukemia
Many tumor cells, in contrast to normal cells, have been shown to require the amino acid glutamine to produce energy for growth and survival. To exploit the dependence of tumors on glutamine, CB-839, a potent and selective inhibitor of the first enzyme in glutamine utilization, glutaminase, will be tested in this Phase 1 study in patients with leukemia.
This study is an open-label Phase 1 evaluation of CB-839 in subjects with leukemia. Part 1 is a dose escalation study to identify the recommended Phase 2 dose as a single agent and in combination with azacitidine. Patients enrolled into Part 2 will be treated with the recommended Phase 2 dose. As an extension of Part 2, patients with relapsed/ refractory or newly diagnosed AML will be treated with CB-839 in combination with azacitidine.
All patients will be assessed for safety, pharmacokinetics (plasma concentration of drug), pharmacodynamics (inhibition of glutaminase), biomarkers (biochemical markers that may predict responsiveness in later studies), and tumor response.
- Being tested
- CB-839, CB-Aza
- Keywords
- leukemia, glutaminase, glutamine
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CB-839Drug
Also called Glutaminase inhibitor
Single-agent CB-839
CB-AzaDrug
Also called combo CB-839 and azacitidine
CB-839 in combination with standard dose azacitidine
| Study group | Role | What they receive |
|---|---|---|
| CB-839 | Experimental | CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity Receives: Drug: CB-839 |
| CB-Aza | Experimental | CB-839 administered as oral capsules twice daily (BID) in combination with azacitidine in 28-day cycles until disease progression or unacceptable toxicity Receives: Drug: CB-839; Drug: CB-Aza |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of CB-839: Incidence of adverse events
Measured: Every 21 days from study start until disease progression or unacceptable toxicity, assessed an expected average of 6 months
Secondary outcomes (3)
Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood
Measured: Study Days 1, 15, and 22
Pharmacodynamics: % inhibition of glutaminase in blood
Measured: Study Days 1 and 15
Clinical Activity: % of Tumor Cells in Bone Marrow
Measured: Every 21 days from study start, assessed for an expected average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2014 (estimated)
- Study startMar 2014
- Primary completionOct 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Calithera Biosciences, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Keith W Orford, MD, PhD, Study director, Calithera Biosciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02071927
- Sponsor's protocol ID
- CX-839-003
- Status last verified
- Feb 2017
- First submitted
- 14 Feb 2014
- Last updated
- 9 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Aden D, Sureka N, Zaheer S, Chaurasia JK, Zaheer S. Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment. Immunology. 2025 Jan;174(1):30-72. doi: 10.1111/imm.13871. Epub 2024 Oct 27.
PubMed 39462179
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Oral Doses of the Glutaminase Inhibitor CB-839 in Patients With Relapsed and/or Treatment-Refractory Leukemia
- ClinicalTrials.gov ID
- NCT02071927
- Acronym / sponsor ID
- CX-839-003
- Keywords
- leukemia, glutaminase, glutamine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Calithera Biosciences, IncIndustry (pharma, biotech, devices)
- Study start
- Mar 2014 (actual)
- Primary completion
- Oct 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 26 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Many tumor cells, in contrast to normal cells, have been shown to require the amino acid glutamine to produce energy for growth and survival. To exploit the dependence of tumors on glutamine, CB-839, a potent and selective inhibitor of the first enzyme in glutamine utilization, glutaminase, will be tested in this Phase 1 study in patients with leukemia.
This study is an open-label Phase 1 evaluation of CB-839 in subjects with leukemia. Part 1 is a dose escalation study to identify the recommended Phase 2 dose as a single agent and in combination with azacitidine. Patients enrolled into Part 2 will be treated with the recommended Phase 2 dose. As an extension of Part 2, patients with relapsed/ refractory or newly diagnosed AML will be treated with CB-839 in combination with azacitidine.
All patients will be assessed for safety, pharmacokinetics (plasma concentration of drug), pharmacodynamics (inhibition of glutaminase), biomarkers (biochemical markers that may predict responsiveness in later studies), and tumor response.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CB-839 | Experimental | Drug: CB-839CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity |
| CB-Aza | Experimental | Drug: CB-839, Drug: CB-AzaCB-839 administered as oral capsules twice daily (BID) in combination with azacitidine in 28-day cycles until disease progression or unacceptable toxicity |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of AML or ALL, relapsed or refractory after at least 1 prior treatment regimen. Newly-diagnosed patients ≥ 60 years old who have refused or are considered unfit for standard chemotherapy regimens or stem cell transplantation are also eligible.
- Patients must have no available approved therapies that confer clinical benefit
- All patients must have bone marrow involvement of their tumor, with documented blast percentage of > 5%.
- Peripheral blood blast count must be ≤ 30,000 cells/µL.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
Key exclusion criteria (11 listed)
- Any other current malignancy
- Patients with acute promyelocytic leukemia (APL)
- Treatment with an unapproved, investigational agent within 21 days of the first dose of study drug
- Allogeneic hematopoietic stem cell transplant or Donor Lymphocyte Infusion within 90 days prior to to the first dose of study drug
- Active GVHD
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CB-839Also: Glutaminase inhibitorSingle-agent CB-839 | Drug | CB-839, CB-Aza |
| CB-AzaAlso: combo CB-839 and azacitidineCB-839 in combination with standard dose azacitidine | Drug | CB-Aza |
Primary outcome
Safety and tolerability of CB-839: Incidence of adverse events
Time frame: Every 21 days from study start until disease progression or unacceptable toxicity, assessed an expected average of 6 months
3 secondary outcomes
Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood
Time frame: Study Days 1, 15, and 22
Pharmacodynamics: % inhibition of glutaminase in blood
Time frame: Study Days 1 and 15
Clinical Activity: % of Tumor Cells in Bone Marrow
Time frame: Every 21 days from study start, assessed for an expected average of 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2017.
- Derived from this study: PubMed 39462179Aden D, Sureka N, Zaheer S, Chaurasia JK, Zaheer S. Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment. Immunology. 2025 Jan;174(1):30-72. doi: 10.1111/imm.13871. Epub 2024 Oct 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith W Orford, MD, PhD study director
Calithera Biosciences
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CB-839 and CB-Aza in people with Acute Myeloid Leukemia (AML) and Acute Lymphocytic Leukemia (ALL), run by Calithera Biosciences, Inc at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of CB-839: Incidence of adverse events (time frame: Every 21 days from study start until disease progression or unacceptable toxicity, assessed an expected average of 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02071927, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2017.